Gene therapy: Hearing restored in a mouse model of human deafness

Nature

December 21, 2017

The CRISPR-Cas9 genome-editing technique has been used to restore hearing in a mouse model of human genetic deafness, reports a paper published in Nature this week. The study highlights the promise of CRISPR-Cas9 as a potential strategy for treating some dominantly inherited hearing-loss diseases.

Genetic factors contribute to nearly half of all deafness cases, yet there are limited treatment options available for inherited hearing loss. David Liu and colleagues designed a lipid-encapsulated Cas9-guide RNA complex that can specifically target a deafness-causing genetic mutation in a mouse model of human deafness.

They show that the system can disrupt the deafness-causing mutant gene, even though it differs from the healthy gene by only one base pair. They then show that injecting the complex into the cochlea of neonatal mice substantially reduces progressive hearing loss. The authors observe higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears compared with uninjected ears or ears injected with complexes that target an unrelated gene. They also observed better acoustic reflex responses in injected compared to uninjected mice.

The authors conclude that this genome-editing strategy may contribute to the future development of a DNA- and virus-free, one-time treatment for certain genetic hearing-loss disorders.